The heart is the center of a person's circulatory system. It includes an electromechanical system performing two major pumping functions. The heart includes four chambers: right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV). The left portions of the heart, including LA and LV, draw oxygenated blood from the lungs and pump it to the organs of the body to provide the organs with their metabolic needs for oxygen. The right portions of the heart, including RA and RV, draw deoxygenated blood from the body organs and pump it to the lungs where the blood gets oxygenated. The efficiency of the pumping functions, indicative whether the heart is normal and healthy, is indicated by measures of hemodynamic performance, such as parameters related to intracardiac blood pressures and cardiac output.
In a normal heart, the sinoatrial node, the heart's natural pacemaker, generates electrical impulses, called action potentials, that propagate through an electrical conduction system to various regions of the heart to excite the myocardial tissues of these regions. Coordinated delays in the propagations of the action potentials in a normal electrical conduction system cause the various portions of the heart to contract in synchrony to result in efficient pumping functions indicated by a normal hemodynamic performance. A blocked or otherwise abnormal electrical conduction and/or deteriorated myocardial tissue cause dysynchronous contraction of the heart, resulting in poor hemodynamic performance, including a diminished blood supply to the heart and the rest of the body. The condition where the heart fails to pump enough blood to meet the body's metabolic needs is known as heart failure.
Myocardial infarction (MI) is the necrosis of portions of the myocardial tissue resulting from cardiac ischemia, a condition in which the myocardium is deprived of adequate oxygen and metabolite removal due to an interruption in blood supply. The adult heart lacks a substantial population of precursor, stem cells, or regenerative cells. Therefore, after MI, the heart lacks the ability to effectively regenerate cardiomyocytes to replace the injured cells in the infarcted areas of the myocardium. Each injured area eventually becomes a fibrous scar that is non-conductive and non-contractile. Consequently, the overall contractility of the myocardium is weakened, resulting in decreased cardiac output. As a physiological compensatory mechanism that acts to increase cardiac output in response to MI, the LV diastolic filling pressure increases as the pulmonary and venous blood volume increases. This increases the LV preload (stress on the LV wall before it contracts to eject blood). One consequence is the progressive change of the LV shape and size, a process referred to as remodeling. Remodeling is initiated in response to a redistribution of cardiac stress and strain caused by the impairment of contractile function in the infarcted tissue as well as in nearby and/or interspersed viable myocardial tissue with lessened contractility due to the infarct. The remodeling starts with expansion of the region of the infarcted tissue and progresses to a chronic, global expansion in the size and change in the shape of the entire LV. Although the process is initiated by the compensatory mechanism that increases cardiac output, the remodeling ultimately leads to further deterioration and dysfunction of the myocardium. Consequently, post MI patients experience impaired hemodynamic performance and have a significantly increased risk of developing heart failure.
It has been proposed that cardiac transfer of bone marrow cells (BMCs) can be used for cardiac tissue repair and regeneration in patients after acute MI (AMI) (Strauer et al., Circulation, 106:1913 (2002); Assmus et al., Circulation, 106:3009 (2002); Wollert et al., Circ. Res., 96:151 (2005)). This concept is supported by the recent randomized controlled bone marrow transfer to enhance ST-elevation infarct regeneration trial (BOOST), showing that intracoronary transfer of unselected autologous BMCs during the early postinfarction period enhances recovery of left ventricular (LV) ejection fraction after 6 months (Wollert et al., Lancet., 364:141 (2004)). The mechanisms by which BMCs enhance functional recovery after AMI remain poorly understood. Regardless, BMC homing in the infarcted myocardium is likely an important early event after intracoronary transfer. In animal models, myocardial homing of transplanted stem and progenitor cells has been monitored by fluorescence or radioactive labeling (Kocher et al., Nat. Med., 7:430 (2001); Aicher et al., Circulation, 107:2134 (2003); Brenner et al., J. Nucl. Med., 45:512 (2004)). However, stem cell transplantation for MI repair is hindered by low levels of cell retention immediately post-transplant. For instance, Hofmann et al. (Circ., 111:2198 (2005)) report that after intracoronary transfer of 18F-FDG-labeled CD34-enriched cells, 14% to 39% of the total activity was detected in the infarcted myocardium. Hayashi et al. (Cell Transplant., 13:639 (2004)) disclose that while 16% of transplanted cells were found within 1 day after intramyocardial injection, other methods of cell delivery yielded levels of retention <5%.
Thus, there is a need for methods and apparatus to improve donor cell retention in vivo.